Gastroesophageal reflux disease (GERD) is a common and vexing problem. Continuous pH monitoring of upright and supine esophageal acid contact times is considered the gold standard for the diagnosis of GERD. Several pharmacologic agents have demonstrated ability to significantly decrease esophageal acid contact. In particular, cisapride, a prokinetic agent, has been shown to be effective in reducing reflux symptoms and esophageal acid contact, resolving endoscopic and histologic esophagitis, and maintaining clinical remission in GERD. Lifestyle modification, and specifically head of bed elevation (HOBE), has also been shown to decrease acid contact time and improve both GERD symptoms and esophagitis. While commonly recommended as a simple yet effective treatment tool, HOBE is often forgotten in clinical practice and has been little studied. This study was designed to compare, via 16 hour continuous pH monitoring, the effect of HOBE by 6 inch bed blocks, cisapride 20 mg po, and the combination of the two, on supine acid reflux in a standardized, placebo-controlled, double blind manner. We conclude that 1) tremendous intra-subject variability exists in the measurement of postprandial reflux despite optimally controlled conditions, 2) postprandial reflux is not a reliable index of GERD, 3) these data call into question the reliability of prolonged pH monitoring in the assessment of GERD, and whether this should indeed be considered the reference diagnostic standard for GERD.